The Role of Spreading Depolarizations in Concussion-like Injuries

扩散去极化在脑震荡样损伤中的作用

• 批准号: 10158658
• 负责人: Russell Morton
• 金额: $ 22.69万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2020-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10158658
• 关键词: Role; Spreading; Depolarizations; Concussion; like

Approximately 3.8 million sports-related concussions occur each year. Diagnosis and treatment of these injuries is usually based on behavioral and cognitive deficits that are not always affected immediately following an injury. The pathophysiology underlying acute phases of concussion deficits are poorly understood but may involve a phenomenon termed spreading depolarization (SD). SDs are large propagating waves of complete depolarization that result in a profound but transient depression of brain activity. Although SDs events have been studied for decades in the context of moderate and severe traumatic brain injuries, only recently have these events been suggested to occur in concussion. These observations and our preliminary data raise the intriguing possibility that SDs underlie some of the short and long-term consequences of concussions. The presence of SDs during a concussion needs to be validated, and it is not yet known whether recurring SDs in the following hours to days following a concussion contributes to persistent cognitive deficits. Our long-term goal is to improve diagnosis and treatments for concussions and to identify strategies to enhance brain recovery and repair following a concussion. The objectives of this proposal are to determine whether SDs contribute to the symptoms of a concussion and identify the deleterious effects of a second concussion prior to brain recovery. My central hypothesis is that SDs are an important underlying mechanism of a concussion that can leave the brain susceptible to subsequent damage from a second impact and/or recurrent SDs resulting in short-term cognitive deficits. The rationale for these studies is that they will directly test the role of SDs as an underlying and targetable mechanism of concussions and the prolonged deficits associated with concussions. SA1: will test the hypothesis that concussion-like impacts initiate SDs. SA2: test the hypothesis that an impact-induced SDs will result in short and long-term deficits in CBF that renders the brain vulnerable to subsequent impacts and damage. SA3: will test the hypothesis that concussion-like impacts produce recurrent SDs in conscious and moving animals and short-term cognitive deficits.

每年约有380万起与运动有关的脑震荡。这些疾病的诊断和治疗 受伤通常是基于行为和认知缺陷，这些缺陷并不总是在受伤后立即受到影响 一个伤口脑震荡缺陷急性期的病理生理机制尚不清楚，但可能 涉及称为扩展去极化（SD）的现象。SD是完整的大传播波 去极化导致大脑活动的深刻但短暂的抑制。虽然SD事件已经 几十年来，在中度和重度创伤性脑损伤的背景下进行了研究，直到最近， 脑震荡中可能发生的事件这些观察和我们的初步数据提出了有趣的 SD是脑震荡的一些短期和长期后果的基础。的存在 脑震荡期间的SD需要验证，目前尚不清楚脑震荡中是否会出现复发性SD。 脑震荡后数小时至数天的持续性认知缺陷。我们的长期 目标是改善脑震荡的诊断和治疗，并确定促进大脑恢复的策略 并在脑震荡后进行修复本提案的目标是确定特殊目的是否有助于 脑震荡的症状，并确定第二次脑震荡的有害影响之前， 复苏我的中心假设是，SD是脑震荡的一个重要的潜在机制， 使大脑容易受到第二次撞击和/或复发性SD的后续损伤，导致短期 认知缺陷这些研究的基本原理是，它们将直接测试SD作为一种 脑震荡的潜在和靶向机制以及与脑震荡相关的长期缺陷。 SA 1：将检验类似脑震荡的撞击引发SD的假设。SA 2：检验撞击引起的 SD将导致CBF的短期和长期缺陷，使大脑容易受到随后的损害。 影响和损害。SA 3：将检验脑震荡样撞击在以下情况下产生复发性SD的假设： 有意识和移动的动物和短期认知缺陷。